Obstructive sleep apnea (OSA) is characterized by the repetitive closure and/or pathologic narrowing of the pharyngeal airway during sleep. Oral devices worn during sleep have been developed to maintain pharyngeal airway patency by moving the mandible and attached pharyngeal tissues forward. However, oral devices have failed to gain widespread acceptance because our understanding of the mechanical effects of mandibular advancement on pharyngeal airway function is inadequate, and predicting which patients will respond prior to construction of a device has not been possible. This research proposal addresses these limitations. We have developed an anatomic model to explain the beneficial effects of mandibular advancement on the pharyngeal airway and will test this model using a unique oral appliance that progressively advances the mandible. In Aim 1 magnetic resonance imaging of the upper airway in anesthetized normal adult subjects will determine the effect of progressive mandibular advancement on pharyngeal airway size and configuration. Based on our anatomic model, we hypothesize that the lower pharyngeal airway will have the greatest increase in size. Aim 2 will test the hypothesis that progressive mandibular advancement stiffens the pharyngeal airway in OSA subjects as measured by: critical airway pressure during NREM sleep and the pressure-area relationship at different levels of the pharyngeal airway under passive conditions. Advancement of the mandible requires some amount of bite opening for the lower incisors to clear the upper incisors. Aim 3 will study the effect of bite opening on pharyngeal airway mechanics during mandibular advancement. Based on our model, we predict that bite opening will stiffen the nasopharyngeal airway. For Aim 4 we have modified our progressive mandibular advancement device into a disposable, universally applicable appliance. This device will be used during a single night's sleep study in OSA subjects to titrate the optimal amount of advancement needed to maintain pharyngeal airway patency. We hypothesize that this titration device will identify those OSA patients who will respond to chronic treatment with an oral device and provide the optimal advancement setting needed in each patient. Aim 4 will also test our hypothesis that the response of OSA patients to oral device treatment is related to the site of pharyngeal airway closure and Pcrit measurements with and without advancement. Understanding the effects of mandibular advancement on pharyngeal airway function will lead to improved design of oral devices and identify physiologic parameters that predict which OSA patients will respond favorably to this potentially important treatment.